Body mass index and glioma risk: A prospective multicenter study.

Background: The association between glioma risk and body mass index (BMI) remains obscure. Methods: This study aimed to assess the association between glioma risk and BMI in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The onset of a total of 269 gliomas was observed during a median follow-up period of 12.04 years. Compared with the normal weight, overweight (HR: 1.05; 95% CI: 0.80, 1.39) and obesity (HR: 0.91; 95% CI: 0.56, 1.39) were not significantly associated with glioma risk. Further analysis showed a nonlinear relationship between glioma risk and BMI in men but not women. The multivariable-adjusted HRs per unit increase in BMI were 0.94 (95% CI: 0.89, 1.00; P = 0.037) in men with BMI >25 kg/m2 and 1.16 (95% CI: 0.98, 1.38; P = 0.075) in men with BMI <25 kg/m2. Conclusion: The present data provide evidence that there may be a nonlinear association between BMI and glioma risk in men. The risk of glioma decreased with increasing BMI among men with BMI >25 kg/m2. Future studies are needed to validate our observation.

Oral Contraceptive and Glioma Risk: A Prospective Cohort Study and Meta-Analysis.

Background: Epidemiological evidence that glioma has a slight male predominance implies that factors associated with sex hormones may play a role in the development of glioma. The association between oral contraceptive (OC) use and glioma risk remains controversial. Method: In the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial of 70,516 women in the USA, Cox proportional hazards regression analyses were adopted to calculate the crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, a meta-analysis combining the PLCO findings with those of other prospective cohorts was performed. Results: During a mean follow-up of ~11.7 years, 110 of 70,516 women aged 50-78 years at baseline were diagnosed with glioma in PLCO studies. Compared with never users, an inverse association of borderline significance was found for OC users (HR 0.67, 95% CI 0.44-1.04, P = 0.074). Analyses assessing glioma risk according to the duration of OC use yielded no significant association. When PLCO was combined with four other prospective studies, there was an inverse association between OC use and glioma risk (HR 0.85, 95% CI 0.75-0.97, I2 = 0.0%). Further dose-response analysis showed a nonlinear, inverse relationship between OC use and glioma risk (P < 0.001). Conclusions: This study provided some evidence of a nonlinear, inverse association between OC use and glioma risk. Future larger studies are warranted to validate this finding.

Parkinson's Disease Risk and Alcohol Intake: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Background: The association between Parkinson's disease (PD) risk and alcohol intake is a controversial topic. Objectives: To systematically assess the association between PD risk and alcohol intake. Methods: PubMed and Embase databases were searched for eligible studies with prospective design on PD risk and alcohol intake. A meta-analysis with a random-effects model and dose-response analysis was performed. Relative risk ratios (RRs) with 95% CIs were calculated. Results: Eleven prospective studies were included. Overall, a higher intake of alcohol was inversely associated with PD risk (RR: 0.81, 95% CI: 0.70-0.95, I 2 = 73.7%). Significant differences existed between the specific types of alcoholic beverages and geographic area. Specifically, a significant association existed for beer (RR: 0.78, 95% CI: 0.65-0.94, I 2 = 0.0%) and studies conducted in Asia (RR: 0.66, 95% CI: 0.55-0.80, I 2 = 37.3%). Dose-response analysis indicated a nonlinear relationship between PD risk and alcohol exposure. No evidence for publication bias was detected. Conclusions: In summary, our meta-analysis suggests that alcohol consumption was associated with a decreased risk of PD, with a nearly U-shaped association. Future studies are warranted to clarify the question of a specific type of alcoholic beverage-dependent association, geographic area effect, and possible threshold effects regarding both the adverse and beneficial effects of alcohol.

Coffee Consumption and Stroke Risk: Evidence from a Systematic Review and Meta-Analysis of more than 2.4 Million Men and Women.

BACKGROUND: Results of stroke risk and coffee consumption are inconclusive. This study aimed to provide an updated systematic review and meta-analysis of the association between coffee consumption and stroke risk. METHOD: Random-effects models were used to pool relative risk estimates (RRs) with 95% confidence intervals (CIs). The highest versus the lowest categories of coffee consumption as well as dose-response analysis with a one-stage robust error meta-regression model (REMR) were assessed for stroke risk. RESULTS: In total, 21 studies including 30 independent cohorts that comprised more than 2.4 million participants were included. The pooled RR with 95% CI for the highest versus the lowest categories of coffee consumption was 0.87 (0.80-0.94) with moderate heterogeneity (I2 = 32.0%). Sensitivity analysis suggested that the influence of each individual data set to an overall result was not significant. As suggested by Begg's funnel plots and Egger tests (p=0.006), some evidence for publication bias was observed. Further analysis with the trim-and-fill method indicated no noticeable harm to our results was generated by any potential bias. Dose-response analysis suggested a nonlinear relationship (U-shape) between stroke risk and coffee (p = 0.0002). The strongest association for stroke (21% lower risk) was found for coffee consumption of 3-4 cups/day and no further reduction in stroke risk was observed with increasing levels of coffee consumption beyond this amount. CONCLUSION: Our study provided evidence of a significant inverse association between coffee consumption and risk of stroke. Future large prospective studies with excellent design are warranted to confirm our findings and provide a more definitive conclusion.

Fish Consumption and Stroke Risk: A Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: Inconsistent results of the association between fish consumption and stroke risk have been indicated in previous epidemiological studies. Therefore, we performed a meta-analysis of prospective cohort studies to estimate the impact of fish consumption on stroke risk. METHODS: The PubMed and EMBASE databases were searched through a computer search. Prospective cohort studies satisfying predetermined inclusion criterion were included. Random-effect model was adopted in this meta-analysis. Analysis of subgroup, sensitivity, publication bias, dose-response, power, and quality of evidence was also conducted. RESULTS: Thirty one publications including 33 independent prospective cohort studies were identified in this meta-analysis. In the primary analysis of the highest versus lowest categories of fish consumption, pooled results indicated that a significant trend toward an inverse association between fish intake and stroke risk (HR = .90, 95% confidence interval [CI] .85-.96). Further subgroup analyses indicated an inverse association was more pronounced in the group of hemorrhagic stroke (HR=.88, 95% CI .80-.96), female (HR =.83, 95% CI .75-.92), and Asia-Pacific (HR = .87, 95% CI .80-.95). Both the funnel plot and Egger tests suggested no evidence of publication bias. Dose-response analysis showed a linear relationship between fish intake and stroke and the risk of stroke decreased by 2%-12% with increasing intake of fish up to 100-700 g/week. According to the NutriGrade scoring system, the level of metaevidence quality was moderate. CONCLUSIONS: Based on current evidence from prospective cohort studies, we concluded that fish consumption was associated with a decreased risk of stroke.

Down-regulated expression of aquaporin-4 in the cerebellum after status epilepticus.

Status epilepticus (SE) is a common neurological condition associated with high rates of mortality and permanent brain injury. SE usually leads to neuronal death which may be accompanied by edema, epileptogenesis and learning impairment. Aquaporin-4 (AQP4), is a transmembrane water channel protein in the neuropil of the central nervous system that has an important role in water transport in the brain; AQP4 expression is altered in many pathological conditions such as changes in the blood- brain barrier and/or astrocytic activation, including seizures. AQP4 was shown to be downregulated in the piriform cortex and the hippocampus after SE. Although it is normally expressed at a high level in the cerebellum, little is known about AQP4 levels in the cerebellum following SE. We addressed this in the present study in a mouse model of pilocarpine-induced SE. We found that AQP4 expression was reduced from 3 h to 3 days after SE, with the levels recovering on day 7. Moreover, mice in the acute post-SE stages exhibited impaired motor coordination and learning. These results indicate that cerebellar damage following SE involves changes in AQP4 expression.

Smoking and Glioma Risk: Evidence From a Meta-Analysis of 25 Observational Studies.

To systematically assess the relationship between smoking and glioma risk.A dose-response meta-analysis of case-control and cohort studies was performed. Pertinent studies were identified by searching database and reference lists. Random-effects model was employed to pool the estimates of the relative risks (RRs) with corresponding 95% confidence intervals (CIs).A total of 19 case-control and 6 cohort studies were included. Overall, compared with those who never smoked, the pooled RR and 95% CI was 0.98 (0.92-1.05) for ever smoker. The subgroups were not significantly different regarding risk of glioma except the group of age at start smoking (RR = 1.17, 95% CI: 0.93-1.48 for age < 20; RR = 1.25, 95% CI: 1.02-1.52 for age ≥ 20). Dose-response analysis also suggested no significant association between smoking and the risk of glioma, although some evidence for a linear relationship between smoking and glioma risk was observed.In conclusion, this meta-analysis provides little support for a causal relationship between smoking and risk of glioma.

Antitumor efficiency of the cytosine deaminase/5-fluorocytosine suicide gene therapy system on malignant gliomas: an in vivo study.

BACKGROUND: Suicide gene therapy, particularly that utilizing the cytosine deaminase/5-fluorocytosine (CD/5-FC) system, represents a novel and attractive methodology of cancer research. Mechanistically, the CD enzyme can convert the antifungal agent 5-FC into the antimetabolite agent 5-fluorouracil (5-FU), thereby killing tumor cells. The purpose of this study was to investigate the antitumor efficiency of the CD/5-FC system in malignant gliomas using a nude mouse model. MATERIAL/METHODS: The eukaryotic expression plasmid pCMV-CD was transfected into U251 malignant glioma cells. Resistant clones (labeled U251/CD cells) were subsequently isolated and further confirmed by reverse transcription polymerase chain reaction (RT-PCR), immunofluoroscence, and immunoblot. Then U251/CD cells were incubated with 5-FC at various concentrations to measure viability ratios as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. 5-FU concentrations in the media were measured by high-performance liquid chromatography (HPLC). Finally, the volumes and weights of tumors from glioma-bearing nude mice after 5-FC intervention were evaluated. RESULTS: The results revealed that the untreated U251 cells were insensitive to 5-FC whereas the U251/CD cells were highly sensitive. Apoptosis and cell death were observed on the U251/CD cells after 5-FC administration. HPLC analysis showed that 5-FU was detected in the U251/CD cell media. These in vivo animal data showed that the volumes and weights of the implanted tumors were dramatically decreased due to cell apoptosis and tumor necrosis. CONCLUSIONS: The in vivo results encourage a further investigation in a controlled trial on the treatment of malignant gliomas via the CD/5-FC gene therapy system.

Effects of CD/5-FC suicide gene therapy system on human malignant glioma cells in vitro.

The purpose of this paper is to investigate the antitumor effects of cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene therapy system on human malignant glioma cells in vitro. The pCMVCD plasmid was constructed through the CD gene insertion in the multicloning site of eukaryotic expression vector pcDNA3.0, and confirmed by restriction endonuclease digestion/gene sequencing. The construct was subsequently transfected into the U251 human malignant glioma cells by using LipofectAMINE2000-mediated method. Resistant clones (named U251/CD cells) were isolated by screening with G418 presence. U251/CD cells were incubated with 5-FC in different concentrations to determine viability ratios (or cytotoxicity assay), measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The concentrations of 5-fluorouracil (5-FU) in the media were measured by high-performance liquid chromatography (HPLC) detector. Our results suggested that the untreated U251 cells were insensitive to 5-FC, with the IC(50) about 6500 micromol/L. After transfection, the IC(50) was dramatically reduced to about 10 micromol/L. Therefore, gene transfection made G418-resistant clones (U251/CD cells) be highly sensitive to 5-FC. HPLC analysis showed that 5-FU was detected in U251/CD cell medium. Study on U251 cells genetically modified by CD gene in vitro will play an essential role in glioma gene therapy in vivo. In conclusion, our results indicated that the CD/5-FC system was feasible to treat glioma.